crossing96/oncoscreening huggingface dataset:
Urothelial cell carcinoma of the bladder in pediatric patients: a systematic review and data analysis of the world literature.	BACKGROUND: Urothelial cell carcinoma (UCC) of the bladder is exceedingly rare in pediatric patients. Limited data are available to guide management in this population. METHODS: The authors systematically searched MEDLINE, Cochrane Library, and Google Scholar (through February 2019) for case reports and series to summarize data regarding presentation, evaluation, management, and follow-up for patients ≤ 18 years diagnosed with UCC of the bladder. Patient-level data were abstracted, and adjusted logistic regression was used to identify factors associated with a combined outcome of recurrence or death. RESULTS: One hundred two articles describing 243 patients from 26 countries met criteria. Average age was 12.5 years, 32.6% were female, 15.3% had medical comorbidities, and 13.2% had known risk factors for bladder cancer. Initial management was transurethral resection in 95.5% of patients, whereas 6.2% required secondary intervention. Tumor stage was TaN0M0 in 86.4% and low grade in 93.4%. Recurrence and death occurred in 8.6% and 3.7%, respectively. Mean time to recurrence or death was 8.6 months (standard deviation [SD] 7.6) for 10.7%. Mean disease free follow-up without recurrence or death was 56.9 months (SD 54.2) for 89.3%. Patients with comorbidities, risk factors, or family history (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.02-5.6); ≥TaN0M0 disease (OR: 6.2, 95% CI: 2.5-15.6); and larger tumors at diagnosis (OR: 1.7, 95% CI: 1.2-2.4) had significantly greater adjusted odds of recurrence or death after initial treatment. CONCLUSION: Based on pooled results, disease recurrence or death occurred in 10.7% of pediatric patients and within 9 months for most and within 32 months for all patients. This may suggest that low-grade and stage UCC of the bladder in pediatric patients can be systematically monitored for at least 3 years. However, prospective evaluation of this clinical strategy is warranted.	bladder
Predictive value of phenotypic signatures of bladder cancer response to cisplatin-based neoadjuvant chemotherapy.	BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive urothelial carcinoma of the bladder confers only a modest survival advantage. Patients with pathologic progression on NAC have poor outcomes related to a delay in definitive surgical management. OBJECTIVE: To characterize the value of epithelial-mesenchymal transition (EMT) effectors and other novel biomarkers to predict response to NAC. METHODS: A tissue microarray was constructed from patients with clinical stage T2 urothelial carcinoma of the bladder using transurethral resection (TUR) specimens (N = 69) and case-matched post-NAC cystectomy specimens (N = 51). Patients were stratified based on pathologic response to NAC and cancer-specific survival. Biomarker expression in TUR specimens was correlated with pathologic response to NAC and clinical outcomes. Phenotypic changes in expression induced by cisplatin-based NAC were characterized in primary TUR and post-NAC cystectomy and lymph node metastasis specimens. RESULTS: Increased expression of mesenchymal markers and actin-cytoskeleton regulators, as well as low apoptosis index, in TUR specimens was associated with pathologic progression on cisplatin-based NAC. Overexpression of N-cadherin and decreased apoptosis was predictive of disease-specific mortality. NAC decreased cofilin phosphorylation and induced a mesenchymal-epithelial transition phenotype. CONCLUSIONS: The epithelial-mesenchymal transition phenotype and actin-cytoskeleton remodeling are associated with pathologic progression on NAC. Chemotherapy induced an mesenchymal-epithelial transition phenotype and decreased cofilin phosphorylation, providing new insights into therapeutic resistance mechanisms. Primary tumors with high apoptosis rates exhibited favorable response to NAC and lower mortality rates, indicating that these tumors may be sensitized to therapy. Further validation will establish these novel signatures as predictors of therapeutic response.	bladder
MicroRNAs: Key Players in Bladder Cancer.	Bladder cancer (BC) is the second highest morbid malignancy of the urinary tract and the fifth most common cancer worldwide. BC is highly malignant with significant morbidity and mortality, especially muscle-invasive BC (MIBC), which has a poor prognosis and frequently recurs after the first resection. Therefore, more sensitive diagnostic tools and effective therapeutic methods are urgently needed. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of protein-coding genes by repressing their translation or cleaving RNA transcripts in a sequence-specific manner. miRNAs play very important roles in regulating genes related to tumorigenesis, tumor development, progression, metastasis and angiogenesis. With the rapid development of high-throughput sequencing technology, an increasing number of miRNAs with aberrant expression between either BC patients and healthy volunteers or between BC tumor tissues and matched peripheral control tissues have been recently examined. The tumor etiopathogenesis must be determined to promote the development of new markers as diagnostic and prognostic tools and targets for bladder tumor therapy, it is therefore vital to elucidate the function of miRNAs with aberrant expression in BC. In the present study, we examined the published data of BC-related miRNAs by reviewing their expression levels, possible functions, potential target genes, related molecular regulatory networks, candidate markers for prognosis and diagnosis, and prospective therapeutic cases, and we summarized the status of research on BC-related miRNAs in recent years.	bladder
Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guérin for patients with high-risk non-muscle invasive bladder cancer.	INTRODUCTION: The initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy. Despite the advancement in surgical technique and postoperative care, the degree of morbidity associated with radical cystectomy remains high, therefore less invasive treatment modalities are desirable. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinoma. We undertook the current study to determine the safety and efficacy of administering pembrolizumab (a monoclonal antibody targeting the interaction between PD-1 and its ligand) in combination with BCG in high-risk NMIBC. METHODS: This is a single-centre phase I safety and efficacy study of pembrolizumab used in combination with intravesicular BCG treatment for subjects with pathologically documented high-risk NMIBC despite having received two courses of induction therapy or BCG treatment followed by maintenance BCG. Fifteen subjects will be enrolled, patients will receive treatment with 200 mg of pembrolizumab every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety of administering pembrolizumab at a fixed dose of 200 mg every 3 weeks in conjunction with intravesicular BCG treatment in patients with high-risk NMIBC who have failed previous treatment. Secondary objectives are to determine the 19 weeks and the 3, 12 and 24 months post-treatment completion complete response rate with combined pembrolizumab and intravesicular BCG therapy in the aforementioned patients. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT02324582.	bladder
Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status.	Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution. Finally, since MDM2 showed differential exon usage, mutations in TP53 and its protein expression have been also studied in the same patients. Our data support that recurrence is epigenetically mediated and favoured by an increase protein expression of TP53, which appears more frequently mutated in advanced stages and grades, being associated to a worse prognosis. Therefore, TP53 mutational status could be used as a potential biomarker in the first stages of NMIBC to predict recurrence and prognosis.	bladder
Expression of Testis-Specific Gene Antigen 10 (TSGA10) is Associated with Apoptosis and Cell Migration in Bladder Cancer Cells and Tumor Stage and Overall Survival in Patients with Bladder Cancer.	BACKGROUND Testis-specific gene antigen 10 (TSGA10) is a tumor suppressor in several types of human malignancy. However, there have been few studies that have investigated the role of TSGA10 in bladder cancer. This study aimed to investigate the expression of TSGA10 in human bladder cancer cell lines and bladder cancer tissues and its effects on patient prognosis. MATERIAL AND METHODS The expression of TSGA10 in 40 tissue samples of bladder cancer and matched normal adjacent bladder tissue, and five human bladder cancer cell lines was assessed by immunohistochemistry, Western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and flow cytometry. The correlation between the expression level of TSGA10 and the clinicopathological features of patients with bladder cancer was analyzed and overall survival (OS) in patients with bladder cancer was determined by Kaplan-Meier curves. RESULTS Upregulation of TSGA10 expression in tissues from patients with bladder cancer was compared with normal adjacent bladder tissue and was significantly correlated with gender, metastasis, lymphovascular invasion, and tumor stage in bladder cancer. In bladder cancer cell lines, down-regulation of TSGA10 reduced cell apoptosis and increased cell migration, and resulted in the formation of an epithelial-mesenchymal transition (EMT) phenotype. Overexpression of TSGA10 resulted in an increased apoptosis rate of tumor cells, reduced cell migration, and contributed to the reversal of the EMT phenotype. CONCLUSIONS These findings support that TSGA10 deserves further study as a potential novel prognostic biomarker in bladder cancer.	bladder
Urothelial Carcinoma of the Bladder, Lipid Cell Variant: Case Report and Literature Review.	The lipid cell variant of urethral carcinoma (UC) is rare and poorly understood clinicopathologically. A nodular tumor detected in the bladder of an 87-year-old man with asymptomatic gross hematuria was transurethrally resected, and high-grade UC, lipid cell variant, was diagnosed pathologically. The tumor cells resembled lipoblasts and contained numerous cytoplasmic vacuoles. Immunohistochemically, the tumor cells stained positive for the epithelial markers CK7, CK20, EMA, CAM5.2, and 34betaE12 and negative for vimentin and S100. Focal positivity for adipophilin was detected in cytoplasm but not in the vacuoles. These findings suggest that the patient had lipid-producing UC.	bladder
Predicting recurrence of nonmuscle-invasive bladder cancer (Ta-T1): A study based on 477 patients.	The aim of this study was to determine clinical recrudescent risk factors of 477 patients with newly discovered nonmuscle-invasive bladder cancer (NMIBC) (Ta-T1) in our hospital, and based on these factors, to establish a recurrence risk prediction model of each NMIBC patient.This study included 477 patients with newly discovered NMIBC (Ta-T1) from January 2012 to December 2016; all patients were treated surgically by transurethral resection of bladder tumor (TURBT). The outcomes of patients were with or without recurrence within 2 years. The nomograms were based on Cox regression analyses, and the calibration curves were founded to evaluate the agreements of the predicted probability with the actual observed probability.Of the 477 patients with NMIBC, 392 were males (82.2%) and 85 were females (17.8%), with median age 64 years. Recurrence was identified in 327 cases (68.6%). The results showed that old age, female sex, smoking history, large size of tumor, multifocal tumors, high grade, and high stage are risk factors for NMIBC recurrence, whereas no significant association was seen between tumor location and recurrence in our study. Based on the results of Cox regression analyses, several independent risk factors, including smoking history, tumor size, multifocal, immediate infusion therapy, T stage, and tumor grade, were used to establish a nomogram to calculate the recurrence probability of each NMIBC patient, and the calibration curve displayed that this nomogram had a great value of prediction.Old age, female sex, smoking history, large size of tumor, multifocal tumors, high grade, and high stage are risk factors for NMIBC recurrence, whereas immediate infusion therapy is a protective factor. And a nomogram was established as a prediction model to calculate the recurrence probability of NMIBC patients.	bladder
Long noncoding RNA HCG22 suppresses proliferation and metastasis of bladder cancer cells by regulation of PTBP1.	Multifarious biological functions of long noncoding RNAs (lncRNAs) have been reported in various cancers including bladder cancer (BCa). This study aims to determine the biological role of a certain lncRNA in BCa. Consistent with the data of The Cancer Genome Atlas database, it was validated that lncRNA HLA complex group 22 (HCG22) was weakly expressed in BCa samples and lowly expressed HCG22 was closely correlated with low overall survival of the BCa patient. To verify the role of HCG22 in BCa progression, functional experiments were carried out in two representative BCa cells (J82 and T24) and the negative effects of HCG22 expression on the cell proliferation, migration, and epithelial-mesenchymal transition were identified. Mechanistically, polypyrimidine tract-binding protein 1 (PTBP1), which was highly expressed in BCa tissues and cell lines, was negatively regulated by HCG22 and the PTBP1-mediated Warburg effect was also obstructed by HCG22. Furthermore, HCG22 modulated the expression of PTBP1 through destabilizing human antigen R (HuR). And functional rescue assays confirmed that HCG22 functioned in bladder cancer through downregulating PTBP1. In conclusion, the present study revealed that HCG22 inhibited BCa progression via the HuR/PTBP1 axis, opening new prospects for potent therapeutic regimens for BCa patients.	bladder
Comparison of Laparoscopic and Robot-assisted Radical Cystectomy for Bladder Cancer: Perioperative and Oncologic Outcomes.	BACKGROUND: The purpose of this study was to compare perioperative and oncologic outcomes between laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) for bladder cancer (BCa). MATERIALS AND METHODS: Patients who underwent LRC or RARC with curative intent for BCa between January 2011 and December 2016 were included. Perioperative, pathologic oncologic data were extracted from our database. Disease-free survival, overall survival, and cancer-specific survival were analyzed using Kaplan-Meier survival curves with log-rank tests. RESULTS: A total of 126 patients underwent LRC and 189 patients underwent RARC during the study period. All the baseline variables were similar between the two groups. Patients undergoing RARC had a significant higher median estimated blood loss (300 mL vs. 200 mL; P = .005), lower rate of 90-day postoperative complications (36.5% vs. 50.0%; P = .017), and higher median direct cost ($15,306 vs. $11,131; P < .001) than LRC. Other perioperative outcomes were similar. No differences were found in pathologic T stage, positive lymph nodes, or positive surgical margin between patients who underwent LRC and RARC. The 5-year disease-free survival, overall survival, and cancer-specific survival rates were 51.9%, 61.0%, and 69.5%, respectively, for all included patients. There were no significant differences in oncologic outcomes between the 2 groups. CONCLUSION: Patients with BCa can be safely managed with LRC and RARC by experienced surgeons. RARC was associated with a reduced rate of postoperative complication but also with higher median estimated blood loss, and higher median direct cost. These findings could be used to guide patient counseling, and treatment selection.	bladder
Increased Incidence of Lung Cancer Among Patients With Superficial Transitional Cell Carcinoma: A Potential Risk Cohort for Lung Cancer Screening.	BACKGROUND: Smoking is a major risk factor for lung cancer (LC) and transitional cell carcinoma of the bladder (TCC). Current recommendations for LC screening do not include TCC as a risk factor for determining screening eligibility. In this study we aimed to evaluate whether TCC patients constitute a population who might benefit from LC screening. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results 18 database was used to determine the incidence, standardized incidence ratio (SIR), and the average time to diagnosis of LC in patients with localized TCC of the bladder (American Joint Committee on Cancer, sixth edition, stages 0-1). RESULTS: On the basis of 91,606 patients with localized TCC, The SIR for LC in men was 1.89 (95% confidence interval [CI], 1.8-1.97), significantly different from the risk for all solid tumors. The SIR for LC in women was 2.43 (95% CI, 2.22-2.65), significantly higher than for men. The 5-year incidence of LC was 3.2%, and the 10-year incidence was 5.94%. The average time to diagnosis of LC was 3.4 years, with >80% of LC cases occurring within 5 years of TCC diagnosis. CONCLUSION: Patients with localized TCC have a higher incidence of LC than the general population. The risk is significantly increased among women compared with men. Considering this increased risk, patients with early stage TCC might stand to benefit from LC screening. Additional differences were noted between male and female TCC patients, which bear further study.	bladder
Incremental Utility of Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer: Quantifying the Relapse Risk Associated with Therapeutic Effect.	The availability of new potent systemic therapies for urothelial carcinoma may change the way we use standard chemotherapy perioperatively. In particular, identifying which patients with muscle-invasive bladder cancer (MIBC) would benefit from adjuvant chemotherapy (AC) is compelling. From a multicenter database we selected 950 patients with cT2-4N0M0 MIBC treated with radical cystectomy (RC), with or without neoadjuvant chemotherapy (NAC), and AC. We used Kaplan-Meier analyses to test 1-yr recurrence-free survival (RFS) rates according to AC use. Nomogram-derived probabilities of 1-yr recurrence after RC were plotted against actual recurrence rates according to AC use. Overall, we did not see evidence of an AC effect on the 1-yr RFS rate (p=0.6). Conversely, the 1-yr RFS rate was higher among patients with pT3-4 or pN1 disease who received AC (75% vs 54%; p<0.001). We were unable to demonstrate a difference between AC and no AC among patients who received prior NAC (1-yr RFS 57% vs 76%; p=0.057). As the most important finding, AC was associated with incremental RFS benefits only for patients with a nomogram-derived 1-yr recurrence probability of >40%. Patient summary: Maximizing disease control with adjuvant chemotherapy was beneficial for patients with muscle-invasive bladder cancer who had a calculated recurrence risk of >40% and did not impact cancer recurrence in lower-risk disease. Therefore, patient stratification using the nomogram available for predicting recurrence is advisable pending external validation.	bladder
Effect of hospital volume on 90-day mortality after radical cystectomy for bladder cancer in Spain.	OBJECTIVE: To investigate 90-day mortality rate of RC for bladder cancer in a nationwide population-based study. DESIGN, SETTING, AND PARTICIPANTS: We used mandatory hospital discharge forms of all patients submitted to RC due to bladder cancer in Spain during 2011-2015 (n = 12,154 in 196 hospitals). At present, a centralization policy for RC has not been issued by the health authorities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We calculated in-hospital, 30-, 60- and 90-day mortality. Average annual RC volume was used as a continuous variable (log-transformed) and also grouped into deciles to identify any potential non-linear relationships. Logistic regression model with mixed effect was performed adjusting for year of surgery, comorbidity, surgical approach, type of admission, age, sex, and hospital size. RESULTS AND LIMITATION: Overall 90-day mortality rate was 6.5%. Lowest mortality rates (3.3% at 90 days) are achieved in hospitals doing more than 38 cases per year. The 90-day adjusted mortality rate is associated with annual average RC volume with a 20.6% decrease per 10 extra RCs/year (95% CI 12.3-28.1% p < 0.001). High Charlson comorbidity index, advanced age, and open surgical approach were the clinical variables associated with higher mortality. CONCLUSIONS: Our study identifies an inverse association between 90-day mortality and hospital volume. High-volume hospitals achieve lower mortality rate within 90 days.	bladder
Depletion of NBR1 in urothelial carcinoma cells enhances rapamycin-induced apoptosis through impaired autophagy and mitochondrial dysfunction.	Rapamycin is well-recognized in the clinical therapeutic intervention for patients with cancer by specifically targeting mammalian target of rapamycin (mTOR) kinase. Rapamycin regulates general autophagy to clear damaged cells. Previously, we identified increased expression of messenger RNA levels of NBR1 (the neighbor of BRCA1 gene; autophagy cargo receptor) in human urothelial cancer (URCa) cells, which were not exhibited in response to rapamycin treatment for cell growth inhibition. Autophagy plays an important role in cellular physiology and offers protection against chemotherapeutic agents as an adaptive response required for maintaining cellular energy. Here, we hypothesized that loss of NBR1 sensitizes human URCa cells to growth inhibition induced by rapamycin treatment, leading to interruption of protective autophagic activation. Also, the potential role of mitochondria in regulating autophagy was tested to clarify the mechanism by which rapamycin induces apoptosis in NBR1-knockdown URCa cells. NBR1-knockdown URCa cells exhibited enhanced sensitivity to rapamycin associated with the suppression of autophagosomal elongation and mitochondrial defects. Loss of NBR1 expression altered the cellular responses to rapamycin treatment, resulting in impaired ATP homeostasis and an increase in reactive oxygen species (ROS). Although rapamycin treatment-induced autophagy by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in NBR1-knockdown cells, it did not process the conjugated form of LC3B-II after activation by unc-51 like autophagy-activating kinase 1 (ULK1). NBR1-knockdown URCa cells exhibited rather profound mitochondrial dysfunctions in response to rapamycin treatment as evidenced by Δψm collapse, ATP depletion, ROS accumulation, and apoptosis activation. Therefore, our findings provide a rationale for rapamycin treatment of NBR1-knockdown human urothelial cancer through the regulation of autophagy and mitochondrial dysfunction by regulating the AMPK/mTOR signaling pathway, indicating that NBR1 can be a potential therapeutic target of human urothelial cancer.	bladder